This study examined whether methadone maintenance treatment decreases drug injection enough to significantly limit HIV-1 transmission among injection drug users (IDU). When HIV-1 seroconversion status among prospectively followed methadone maintenance clients was analyzed by treatment retention, 1/56 (2%) of those who remained continuously in treatment seroconverted while 8/42 (19%) of those whose methadone treatment was interrupted seroconverted. When controlled for length of follow up, the difference in seroconversion rate was not statistically significant. Subjects in continuous treatment had a seroconversion rate of 0.7 per 100 person years (95% Confidence Interval [CI] = 0.1, 5.3) and those with interrupted treatment a rate of 4.3 per 100 person years (95% CI = 2.2, 8.6). Subjects in continuous treatment reported less needle sharing (p less than 0.0002), fewer needle sharing partners (p less than 0.002), fewer sexual partners (p less than 0.03), and were more likely to be women (p less than 0.01). These data indicate the need for larger studies to evaluate both client and drug treatment program characteristics which might concomitantly increase treatment retention and decrease HIV-1 risk.